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Identification and evaluation of novel serum autoantibody biomarkers for early diagnosis of gastric cancer and precancerous lesion

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Abstract

Purpose

Early diagnosis is crucial for optimal prognosis of gastric cancer (GC). Hereby, we aimed to identify novel serum autoantibody-based biomarkers for precancerous lesion (PL) and early GC.

Methods

We performed serological proteome analysis (SERPA) combined with nanoliter-liquid chromatography combined with quadrupole time of flight tandem mass spectrometry (Nano-LC-Q-TOF-MS/MS) to screen for GC-associated autoantibodies. The identified autoantibodies were analyzed for potential detection value for PL and GC by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curves analysis was conducted to evaluate the accuracy of the biomarkers.

Results

We identified seven candidates, such as mRNA export factor (RAE1), Nucleophosmin 1 (NPM1), phosphoglycerate kinase 1 (PGK1), and ADP-ribosylation factor 4 (ARF4). Antibodies against all seven proteins were present at higher levels in sera from 242 patients (51 PL, 78 early GC, 113 advanced GC) compared with sera from 122 healthy individuals. RAE1-specific autoantibody discriminated best between patients at different GC stages, with area under the curve (AUC) values of 0.710, 0.745, and 0.804 for PL, early GC, and advanced GC, respectively. Two predictive models composed of gender, RAE1, PGK1, NPM1, and ARF4 autoantibodies (Model 2 for PL) and of age, gender, RAE1, PGK1, and NPM1 autoantibodies (Model 3 for early GC) had improved diagnostic efficiencies, with AUCs of 0.803 and 0.857, sensitivities of 66.7% and 75.6%, and specificities of 78.7% and 87.7%, respectively.

Conclusion

The identified serum tumor-associated autoantibodies (TAAbs) may have good potential for early detection of GC and PL.

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Data availability

All datasets presented in this study are included in the article/Supplementary Material.

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Acknowledgements

We thank the patients for providing their samples for this study. We acknowledge the Beijing Friendship Hospital, Capital Medical University, and the Cancer Hospital, Chinese Academy of Medical Sciences for sample collection. We thank Anne M. O’Rourke, PhD, from Liwen Bianji (Edanz) (http://www.liwenbianji.cn), for editing the English text of a draft of this manuscript.

Funding

This work was funded by Grants from the National Major Science and Technology Projects of China (No.2017ZX10201201) and the Digestive Medical Coordinated Development Center of Beijing Municipal Administration of Hospitals (No. XXZ0103).

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Author notes

  1. Qianyu Zhu, Pingping He, Cuiling Zheng, and Zhibin Chen have contributed equally to this work and share first authorship.

Authors and Affiliations

  1. Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China

    Qianyu Zhu, Pingping He, Zhibin Chen, Saiping Qi, Donghu Zhou, Yanmeng Li, Qin Ouyang, Huaduan Zi, Hengcheng Tang & Jian Huang

  2. Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China

    Cuiling Zheng

  3. Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China

    Jie Xing & Shengtao Zhu

  4. Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China

    Yibin Xie

  5. Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China

    Jiansong Ren

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  1. Qianyu Zhu
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Contributions

JR, SZ, and JH contributed to the project design. CZ, JX, and YX participated in collecting samples and clinical analysis. QZ, PH, ZC, SQ, QO, HZ, and HT participated in the implementation of the experiments. QZ and PH contributed to drafting the manuscript. DZ, YL, and JH contributed to revising the manuscript critically. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Yibin Xie, Shengtao Zhu, Jiansong Ren or Jian Huang.

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Conflict of interest

The authors declare no conflict of interest.

Institutional review board statement

The study was conducted in accordance with the Declaration of Helsinki, and approved by the Ethics Committee of the Beijing Friendship Hospital/Capital Medical University (No.2018-P2-058-01) and Cancer Hospital/Chinese Academy of Medical Sciences (No.14-067/857).

Informed consent

Informed consent was obtained from all subjects involved in the study. Written informed consent has been obtained from the patients to publish this paper.

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Zhu, Q., He, P., Zheng, C. et al. Identification and evaluation of novel serum autoantibody biomarkers for early diagnosis of gastric cancer and precancerous lesion. J Cancer Res Clin Oncol 149, 8369–8378 (2023). https://doi.org/10.1007/s00432-023-04732-z

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